Difference between revisions of "Part:BBa K4165006"
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/td28rev.jpg" style="margin-left:350px;" alt="" width="250" /></p> | <p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/td28rev.jpg" style="margin-left:350px;" alt="" width="250" /></p> | ||
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+ | <p style=" font-weight: bold; font-size:14px;"> Docking </p> | ||
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+ | Docking was performed using three different algorithms (Lightdock, Cluspro, and Galaxy web server) to test the interaction and binding affinity of TD28REV to both tau PHF filament and amyloid beta aggregates, this was followed by ranking of docked models and selection of models with the lowest free energy of binding. | ||
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+ | <p style=" font-weight: bold; font-size:14px;"> TD28REV vs Tau seed (PHF): </p> | ||
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+ | ΔG = -170.825 | ||
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+ | <p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/topphfvstd28rev.png" style="margin-left:350px;" alt="" width="250" /></p> | ||
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+ | <p style=" font-weight: bold; font-size:14px;"> TD28REV vs Amyloid beta: </p> | ||
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+ | ΔG = -40.34 | ||
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+ | <p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/topabvstd28rev.png" style="margin-left:350px;" alt="" width="250" /></p> | ||
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Revision as of 19:24, 4 October 2022
TD28rev (Tau binding peptide)
A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 of tau fibrils.
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
Usage and Biology
A short synthetic peptide acquired by mirror image phage display for binding to tau fibrils at its seed sequence ‘VQIVYK’ called the PHF6. The aggregation of microtubule-associated tau protein starts at this seed to form neurofibrillary tangles inside the brain, which are the main cause of Alzheimer’s disease (AD). Accordingly, this peptide would be suitable to act as our targeting domain for the aggregations.
Dry Lab characterization
Modeling
We modeled the peptide with (Alphafold2, Apptest, iTASSER, and trRrosetta) and our top model was obtained from Apptest scoring 6 out of 6 according to our quality assessment code.
Docking
Docking was performed using three different algorithms (Lightdock, Cluspro, and Galaxy web server) to test the interaction and binding affinity of TD28REV to both tau PHF filament and amyloid beta aggregates, this was followed by ranking of docked models and selection of models with the lowest free energy of binding.
TD28REV vs Tau seed (PHF):
ΔG = -170.825
TD28REV vs Amyloid beta:
ΔG = -40.34
References
Dammers, C., Yolcu, D., Kukuk, L., Willbold, D., Pickhardt, M., Mandelkow, E., ... & Funke, S. A. (2016). Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease. PLoS One, 11(12), e0167432.